16q21 is critical for 16q deletion syndrome

A 1-year-old girl with an interstitial deletion of the long arm of chromosome 16 is reported. She was characterized by a distinct craniofacial dysmorphism, meningoencephalocele, mild hydrocephalus, short neck, broad great toes and abnormally positioned toes. High resolution GTG and RBG banding analyses revealed a karyotype: 46,XX,del(16) (q13q22) de novo. An analysis of the smallest region of overlap revealed that the critical band region for 16q deletion syndrome is 16q21.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Two cases of 16q12.1q21 deletions and refinement of the critical region

Interstitial deletions of 16q chromosome including 16q12.1q21 region are very rare, with only three cases reported to date. Main clinical features include dysmorphisms, short stature, microcephaly, eye abnormalities, epilepsy, development delay, intellectual disability, and autism spectrum disorder.We report two independent subjects with 16q12.1q21 deletion syndrome presenting with dysmorphic facial features, developmental delay, strabismus, and aggressive behavior. A minimal region of overlap spanning 1.7 Mb on chromosome 16, including IRX5, GNAO1, and NUDT21 genes was shared among these two cases and those previously reported. This minimal region of overlap suggests the potential pathogenic role of these genes, previously implicated in diseases of the central nervous system.     

Reassessment of the 12q15 deletion syndrome critical region

Interstitial deletions of the long arm of chromosome 12 are rare and only few cases have been reported in literature so far, with different phenotypic features related to size and gene content of deleted regions. Five patients reported a 12q15-q21 deletion, sharing a 1.3 Mb small region of overlap (SRO) and presenting with developmental delay, nasal speech and mild dysmorphic features.We identified by microarray analysis a new case of 12q15 deletion. Our patient clinical features allow the refinement of the SRO to CNOT2, KCNMB4, and PTPRB genes, improving genotype-phenotype correlations.     

Deletion 5q35.3

We report on a 15-month-old boy with a de novo deletion of the terminal band of 5q, macrocephaly, mild retrognathia, anteverted nares with low flat nasal bridge, telecanthus, minor earlobe anomalies, bell-shaped chest, diastasis recti, short fingers, and mild developmental delay. © 1994 Wiley-Liss, Inc.     

Interstitial deletion of chromosome 5 in a neonate due to maternal insertion,ins(8;5)(p23;q33q35)

We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months. Am. J. Med. Genet. 86:289–293, 1999. © 1999 Wiley-Liss, Inc.     

Clinical phenotype associated with terminal 2q37 deletion

Three children with deletions of the terminal portion of the long arm of chomosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.     

Interstitial deletion 2q31→q33

We present an 8-month-old female with severe retardation of growth and development, multiple congenital anomalies, and an interstitial deletion del(2)(q31→q33) including results of cytogenetic and gene marker studies. The manifestations of this infant are compared with those of four other known patients with a partial del(2q).     

Second case report of del(4) (q25q27) and review of the literature

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.     

Interstitial deletion of chromosome 2q associated with ovarian dysgenesis

In the present report we describe a girl with mental retardation, Dandy-Walker malformation, craniofacial anomalies, cardiac defect, and ovarian dysgenesis associated with an interstitial deletion of chromosome 2. The interstitial deletion in the proband was associated with an apparently balanced translocation involving chromosomes 2 and 7 in the father.     

Chromosome deletion 1q42-43

We report on a newborn male and a female of 3 years 9 months with de novo 1q42 or 43-qter deletions. These cases are compared with ten other reported cases.     

A case of de novo interstitial deletion of chromosome 5(q33q34)

The present paper describes a girl with a small de novo deletion of chromosome 5(q33q34). Fluorescence in situ hybridisation with locus specific probes was used to define the extent of this deletion. Clinical features in this patient are microcephaly, dysmorphic facial features such as epicanthus, small biparietal distance and retrognathia, four-finger lines on both hands and mild mental retardation.     

A case of retinoblastoma, associated with histiocytosis-X and mosaicism of a deleted D-group chromosome (13q14→q31)

A previously unpublished association of retinoblastoma and histiocytosis-X is described in a girl. In addition, chromosome analysis revealed a mosaicism of normal and abnormal mitoses. A deleted D-group chromosome (13q14-q31) was present.     

5q21 deletion is often heterogeneous in prostate cancer

Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG‐negative (28%) than in ERG‐positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG‐positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.     

Holoprosencephaly associated with an apparent isolated 2q37.1→2q37.3 deletion

A female infant survived 5½ hours after delivery at 33 weeks gestation. Autopsy showed a lobar variant of holoprosencephaly (HPE). Cytogenetic analysis revealed a 2q37.1→2q37.3 deletion. This case represents the fourth reported case of HPE associated with partial monosomy 2q37 and the first with an apparent isolated 2q37 deletion. Chromosome segment 2q37.1→2q37.3 may harbor yet another locus important in forebrain development, which, when disrupted, can lead to brain malformations within the HPE spectrum. © 2001 Wiley‐Liss, Inc.